Spinal cord stimulation to treat pain

ABSTRACT

A system and method for treating pain without paresthesia by spinal cord stimulation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/550,196, filed Jul. 16, 2012, now U.S. Pat. No. 8,934,981, which is acontinuation of U.S. patent application Ser. No. 12/047,104, filed Mar.12, 2008, now U.S. Pat. No. 8,224,453, which claims the benefit of U.S.Provisional App. Ser. No. 60/895,061, filed Mar. 15, 2007, thedisclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present application relates the fields of medicine, morespecifically neuromodulation. In certain aspects, the presentapplication relates to neuromodulation for medical treatment, and moreparticularly to stimulating neuronal tissue in the spinal cord fortreating pain without paresthesia.

BACKGROUND

Spinal cord stimulation (SCS) has been used as a treatment for chronicpainful conditions for approximately thirty years. Commonly, SCS is usedto alleviate pain after failed surgery, pain due to neuropathies, orpain due to inadequate blood flow. SCS originated shortly after thepublication of Melzack and Wall's “Gate Control Theory.” The theoryessentially states that mutual inhibitory connections exist between slowconducting nociceptive C-fiber sensory neurons and fast conductingnon-nociceptive Aβ fiber sensory neurons. Whether or not this mutualinhibition is direct and/or indirect via inhibitory interneurons is notcompletely understood, but it is known that this inhibitory effect canbe seen at the level of the second order dorsal horn neurons thatproject both nociceptive and non-nociceptive sensory information to thebrain. Thus, the therapeutic effect of spinal cord stimulation may actaccording to the principals of Gate Control Theory or it may beefficacious due to as yet poorly understood mechanisms (e.g., inhibitoryinterneuron activation, pain perception modulation in the brain).Regardless of the specific mechanism, those skilled in the art havestimulated non-nociceptive fibers as a therapy to alleviate painsymptoms in cases of chronic pain.

In practical application, electrodes are implanted within the epiduralspace for delivery of electrical stimulation. The electrodes are coupledto a pulse generator which generates high frequency stimulation pulses.Specifically, conventional spinal cord stimulation applies stimulationpulses to neural tissue of the dorsal column in a regular pattern witheach pulse being separated by a fixed inter-pulse interval that definesthe stimulation frequency. It is believed that high frequency tonicstimulation acts as a “digital lesion” which prevents communication ofpain signals to the thalamus of the patient. Specifically, highfrequency stimulation has been observed to prevent the perception ofcertain types of pain by patients. Instead of perceiving pain, the highfrequency electrical stimulation causes other sensation signals to reachthe thalamus whereby the patient experiences a tingling sensation knownmedically as paresthesia. Although the paresthesia can be uncomfortableor even painful in patients, the paresthesia is usually substantiallymore tolerable than the pain previously experienced by the patients and,hence, is considered an acceptable negative side-effect.

BRIEF SUMMARY

The claimed material comprises a therapeutic system for treating painhaving a surgically implanted device in communication with a spinal cordtreatment site. The device can include a distal probe, such as, forexample, an electrode assembly or electrical stimulation lead. Theproximal end of the probe may be coupled to an electrical signal source,which, in turn, may be operated to stimulate the predetermined dorsalcolumn treatment site. Later embodiments stimulate the dorsal column orposterior funiculus, which is located between the posterior medianseptum and the posterior horn in the spinal column.

The foregoing has outlined rather broadly the features and technicaladvantages of the claimed material in order that the detaileddescription that follows may be better understood. Additional featuresand advantages will be described hereinafter which form the subject ofthe claims. It should be appreciated that the conception and specificembodiment disclosed may be readily utilized as a basis for modifying ordesigning other structures for carrying out the same purposes. It shouldalso be realized that such equivalent constructions do not depart fromthe material set forth in the appended claims. The novel features whichare believed to be characteristic of the claimed material, both as toits organization and method of operation, together with further objectsand advantages will be better understood from the following descriptionwhen considered in connection with the accompanying figures. It is to beexpressly understood, however, that each of the figures is provided forthe purpose of illustration and description only and is not intended asa definition of the limits of the claimed material.

BRIEF DESCRIPTION OF THE DRAWING

For a more complete understanding of the claimed material, reference isnow made to the following descriptions taken in conjunction with theaccompanying drawing, in which:

FIG. 1 illustrates an exemplary burst stimulation pattern;

FIG. 2 illustrates an exemplary spike ramping;

FIGS. 3A-3B illustrates pain scores. FIG. 3A shows scores from thevisual analogue scale (VAS) and FIG. 3B shows scores from a McGillShortform during pre-operative, tonic and burst stimulation;

FIG. 4 is a block diagram of steps according to a method for treatingpain using a spinal cord stimulation system;

FIGS. 5A-5B illustrate example stimulation systems for electricallystimulating the spinal cord;

FIGS. 6A-6I illustrate example electrical stimulation leads that may beused to electrically stimulate the spinal cord; and

FIG. 7 illustrates an example method of implanting the stimulationsystem of FIGS. 5A-5B with leads in communication with the dorsal columnof the spinal cord.

DETAILED DESCRIPTION I. Definitions

Unless defined otherwise, technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the claimed material belongs. The following terms aredefined below.

As used herein, the use of the word “a” or “an” when used in conjunctionwith the term “comprising” in the claims and/or the specification maymean “one”, but it is also consistent with the meaning of “one or more,”“at least one”, and “one or more than one”. Still further, the terms“having”, “including”, “containing” and “comprising” are interchangeableand one of skill in the art is cognizant that these terms are open-endedterms.

As used herein, the term “in communication” refers to the stimulationlead being adjacent, in the general vicinity, in close proximity, ordirectly next to or directly on the predetermined stimulation site.Thus, one of skill in the art understands that the lead is “incommunication” with the predetermined site if the stimulation results ina modulation of neuronal activity. The predetermined site may beselected from the group consisting of the spinal cord, and the dorsalcolumn of the spinal cord which may include the spinal cord areacorresponding to cervical vertebral segments C1 to C8, thoracicvertebral segments T1 to T12, or lumbar vertebral segments L1 and L2.One of ordinary skill in the art will understand that the spinal cordnormally terminates at the second lumbar vertebrae L2. However, incertain subjects the spinal cord may terminate before or after the L2vertebrae segment, and the claimed material is intended for use alongthe entire length of the spinal cord regardless of length.

As used herein, “spinal cord,” “spinal nervous tissue associated with avertebral segment,” “nervous tissue associated with a vertebral segment”or “spinal cord associated with a vertebral segment or level” includesany spinal nervous tissue associated with a vertebral level or segment.Those of skill in the art are aware that the spinal cord and tissueassociated therewith are associated with cervical, thoracic and lumbarvertebrae. As used herein, C1 refers to cervical vertebral segment 1, C2refers to cervical vertebral segment 2, and so on. T1 refers to thoracicvertebral segment 1, T2 refers to thoracic vertebral segment 2, and soon. L1 refers to lumbar vertebral segment 1, L2 refers to lumbarvertebral segment 2, and so on, unless otherwise specifically noted. Incertain cases, spinal cord nerve roots leave the bony spine at avertebral level different from the vertebral segment with which the rootis associated. For example, the T11 nerve root leaves the spinal cordmyelum at an area located behind vertebral body T8-T9 but leaves thebony spine between T11 and T12.

As used herein, the use of the term “dorsal column” refers to conductingpathways in the spinal cord that are located in the dorsal portion ofthe spinal cord between the posterior horns, and which comprisesafferent somatosensory neurons. The dorsal column is also known as theposterior funiculus.

As used herein, the use of the words “epidural space” or “spinalepidural space” is known to one with skill in the art, and refers to anarea in the interval between the dural sheath and the wall of the spinalcanal.

As used herein, the term “neuronal” refers to a neuron which is amorphologic and functional unit of the brain, spinal column, andperipheral nerves.

As used herein, the term “somatosensory system” refers to the peripheralnervous system division comprising primarily afferent somatic sensoryneurons and afferent visceral sensory neurons that receive sensoryinformation from skin and deep tissue, including the 12 cranial and 21spinal nerves.

As used herein, the term “stimulate” or “stimulation” refers toelectrical, chemical, heat, and/or magnetic stimulation that modulatesthe predetermined sites in the nervous system.

As used herein, the term “treating” and “treatment” refers to modulatingcertain areas of the spinal cord so that the subject has an improvementin the disease, for example, improvements in pain without paresthesia.Beneficial or desired clinical results include, but are not limited to,alleviation of symptoms, diminishment of extent of disease, stabilized(i.e., not worsening) state of disease, delay or slowing of diseaseprogression, amelioration or palliation of the disease state, andremission (whether partial or total), whether detectable orundetectable. One of skill in the art realizes that a treatment mayimprove the disease condition, but may not be a complete cure for thedisease.

As used herein, the terms “spike”, “action potential”, and “pulse”, allrefer to a rapid rise and fall of voltage in a specified region ofspace. One skilled in the art realizes that the term action potentialgenerally refers to a spike or pulse that is produced by a neuron. Oneskilled in the art also recognizes that the term action potential canalso be expanded to include the spiking of cells in other excitabletissues. The terms spike and pulse may refer to action potentialsproduced by neurons and other excitable cells and may also refer toartificial stimulations that mimic the features of action potentials incells or groups of cells. The terms “inter-spike interval” or“inter-pulse interval” refer to the period of time between two actionpotentials, spikes, or pulses. However, one of skill in the art alsorealizes that naturally occurring spikes do not necessarily occur at afixed rate; this rate can be variable. In such cases an averageinter-spike interval may be used to define the average period of timebetween consecutive action potentials, spikes, or pulses in a series.

As used herein, the term “burst” refers to a rapid succession of two ormore neuronal action potentials or external stimuli in the approximatefrequency range of 50-1000 Hz (Beurrier et al., 1999) that, possibly,occurs during a ‘plateau’ or ‘active phase’, followed by a period ofrelative quiescence called the ‘silent phase’ (Nunemaker, CellscienceReviews Vol 2 No. 1, 2005). A burst stimulation may occur from a plateauor elevated pulse amplitude applied by the pulse stimulator. Also, ahyper-polarizing or other pre-conditioning pulse may precede the burst.A charge balancing pulse or pulses may be applied within the burst or atthe end of the burst. A burst spike may be described as a spike that ispreceded or followed by another spike within a short time interval ofapproximately (0.1-10 msec) (Victor Matveev, Differential Short-termSynaptic Plasticity and Transmission of Complex Spike Trains: to Depressor to Facilitate? Cerebral Cortex, Volume 10, issue 11, Pages 1143,November 2000). Those skilled in the art recognize that a burst canrefer to a plurality of groups of spike pulses. In some embodiments, aburst may be a period in time in which two or more spikes occurrelatively rapidly, such that the spikes summate in the dendrites orcell body of a neuron in a non-linear fashion. The period of timebetween the beginning of a burst and the end of the same said burst isthe “intra-burst interval”. The period of time between two bursts is the“inter-burst interval”. For example, 1 milliseconds to about 5 seconds,more preferably, about 10 milliseconds to about 300 milliseconds. Insome embodiments, the burst stimulus may comprise pulse amplituderamping, for example increasing the amplitude of successive pulseswithin an individual burst. One skilled in the art is also aware thatburst firing can also be referred to as phasic firing, rhythmic firing(Kwang-Hyuk Lee, An inegration of 40 Hz Gamma and phasic arousal:novelty and routinization processing in schizophrenia, ClinicalNeurophysiology, Volume 112, Issue 8, Pages 1499-1507 August 2001),pulse train firing, oscillatory firing and spike train firing, all ofthese terms used herein are interchangeable. While not being bound bytheory, one of skill in the art is also aware that the burst stimuluscan also be defined as amplitude modulation (AM) and/or transientfrequency modulation (FM) as it relates to the communication fields.

As used herein, the term “tonic” as well as the phrases “tonic firing”,“tonic spike”, “tonic pulse”, or “tonic mode” refers to any process inwhich the firing pattern can be accurately described as a series ofsingle spikes of a given frequency or with a given inter-spike interval,wherein the inter-spike interval may be fixed or variable.

The term “pain” as used herein refers to an unpleasant sensation. Forexample, the subject experiences discomfort, distress or suffering. Itis known to one skilled in the art that various painful conditions maybe classified according to broadly opposing or otherwise usefulcategories. Examples of opposing categories include; nociceptive painversus non-nociceptive pain, and acute pain versus chronic pain.Examples of other common categories of pain used by those skilled in theart include neuropathic pain and phantom pain.

The term “nociception” as used herein refers to the transduction ofnoxious or potentially injurious stimuli into a sensation.

The term “nociceptive pain” as used herein refers to pain caused byactivity in primary sensory pain fibers in the peripheral nervoussystem. Neurons in the peripheral nervous system that typically respondto noxious or painful stimuli are commonly referred to as nociceptors ornociceptive neurons. Yet further, the nociceoptive pathways extend tothe somatosensory cortex.

The term “non-nociceptive pain” as used herein refers to pain caused byactivity in neurons in the central nervous system. Examples of neuronsin the central nervous system that may cause non-nociceptive paininclude neurons in the dorsal horn of the spinal cord such asinterneurons and projection neurons, or neurons in parts of the brainknown to be involved in pain sensation such as the rostral ventromedialmedulla (RVM) and the periaqueductal grey (PAG).

The term “acute pain” as used herein refers to pain that is transient innature or lasting less than 1 month. Acute pain is typically associatedwith an immediate injurious process such as soft tissue damage,infection, or inflammation, and serves the purpose of notifying theanimal of the injurious condition, thus allowing for treatment andprevention of further injury.

The term “chronic pain” as used herein refers to pain that lasts longerthan 1 month or beyond the resolution of an acute tissue injury or isrecurring or is associated with tissue injury and/or chronic diseasesthat are expected to continue or progress. Examples of chronic diseasesthat are expected to continue or progress may include cancer, arthritis,inflammatory disease, chronic wounds, cardiovascular accidents, spinalcord disorders, central nervous system disorder or recovery fromsurgery.

The term “neuropathy” as used herein refers to any condition thatadversely affects the normal functioning of the nervous system.Neuropathies can originate anywhere in the central or peripheral nervoussystem, but only in some cases does this produce neuropathic pain.

The term “neuropathic pain” as used herein refers to pain that resultsfrom damage to or abnormal function of the nervous system itself. It mayexist independently of any form of tissue injury outside of the nervoussystem. Examples of conditions that may lead to neuropathic pain includedisease (e.g., HIV, Herpes, Diabetes, Cancer, autoimmune disorders),acute trauma (surgery, injury, electric shock), and chronic trauma(repetitive motion disorders, chemical toxicity such as alcohol,chemotherapy, or heavy metals).

The term “phantom pain” as used herein refers to a condition whereby thepatient senses pain in a part of the body that is either no longerphysically present due to amputation, or is known to be completelyinsensate due to total peripheral nerve destruction.

The term “hyperalgesia” as used herein refers to an increasedsensitivity to nociceptive or painful stimuli. The term “allodynia” asused herein describes a condition whereby normally non-noxious stimuliare perceived as painful. Both hyperalgesia and allodynia can be dividedinto primary and secondary categories or conditions. Primaryhyperalgesia/allodynia is an increase in sensitivity to painful andpreviously non-painful stimuli in a region of the body that hasundergone tissue injury. Secondary hyperalgesia/allodynia is an increasein pain sensitivity globally and requires descending input into theperiphery from various pain processing centers in the brain.

II. Experimental Section A. Example 1 Introduction

Some neurons fire in packets of action potentials followed by periods ofquiescence (bursts) while others, within the same stage of sensoryprocessing, fire in a tonic manner. Burst and tonic firing might beprocessing information in parallel in certain sensory systems (Ozwald etal., 2004; Chacron et al. 2004). Up to now all neuromodulation devicesused in humans were using tonic stimuli, whether magnetic or electrical.

The applicants recently initiated electrical stimulation protocolsconsisting of intra-burst inter-pulse frequencies of 500 Hz andinter-burst frequencies of 40 Hz, using electrodes implanted on thedorsal column as a treatment for chronic pain.

It was noted that during cervical dorsal column stimulation that noparesthesias were induced at stimulation parameters required for symptomsuppression. Using the same stimulation design, the applicants nowpresent the first cases of dorsal column stimulation for painsuppression, wherein pain suppression can be achieved without inducingparesthesias, which was previously a universal side-effect of dorsalcolumn stimulation.

Methods

Patients with intractable pain were implanted with dorsal columnelectrodes. Before and after treatment patients were asked to measuretheir pain sensation using the Visual Analog Pain Scale (VAS) in whichthe pain may be assigned a value between zero and ten with zerorepresenting no pain and ten representing maximum pain experience(Huskisson, 1982). Results of pain suppression with tonic stimulationwere compared to burst stimulation, as well as the presence or absenceof paresthesia at stimulation parameters used to obtain painsuppression. All patients were implanted extradurally with paddleelectrodes (Lamitorode 44, ANS Medical, Plano, Tex., USA), either on thecervical dorsal column at the level of C2 for intractablecervicobrachialgia or on the thoracic dorsal column at the level of T11for intractable Iumboischialgia. Details of the patients are shown belowin Table 1.

TABLE 1 Inter-Burst Intra-Burst Pulse Pulse VAS Pain Scores VAS PainScores Patient Freq (Hz) Freq (Hz) (#) Width (μS) Before After 1 40 5005 1000 VAS C2 area VAS pain: 0 right: 8 VAS pressure: 0 (after 10min)/VAS 2 40 500 5 1000 VAS Left Leg: 8 All VAS: 0 VAS Right Leg: 8 VASBack: 8 3 40 500 5 1000 VAS Arms: 8 VAS:0 Ri Arm, Ri Sch, Le Hnd, +improved mobility hnd, No positional changes, relaxation biceps 4 40 5005 1000 VAS: Legs 8 Total system VAS: Back 8 explanted due to infection 540 500 5 1000 VAS Left Leg: 9 With Tonic Stim: VAS Right Leg: 9 VASLegs: 0 VAS Back: 9 VAS Back 9 Burst Stim: VAS Legs: 0 VAS Back: 0 6 40500 5 1000 VAS Back: 6 Tonic Stim: (range 3-8) VAS leg: 0-2 VAS leftleg: VAS back: 6/5% (range 3-8) of 3 mA Burst Stim: VAS back: 2 VAS Leg:0 7 40 500 5 1000 VAS R Lower Leg VAS 1-2 (peroneous area, ankle, foot:8 8 40 500 5 1000 Infection Infection 9 40 500 5 1000 VAS: 8 (Legs, ftVAS: 0 and lower left back) 10 40 500 5 1000 VAS Legs: 9 Tonic Stim VASBack: 8 VAS Legs: 2 VAS Back: 8 Burst Stim: VAS Legs: 0 VAS Back: 0

All patients underwent a burst stimulation with an inter-burst intervalof 40 Hz whereby each burst consisted of 5 spikes having 1 ms pulsewidth, 1 ms interspike interval in a charged balanced way as illustratedin FIG. 1 . The burst stimuli were delivered by an 8 channel digitalneurostimulator (DS8000, World Precision Instruments, Hertfordshire,England/Sarasota, Fla., USA), capable of delivering tonic and burst modestimulation.

If the externally delivered burst stimulation was successful inobtaining pain suppression, a commercially available internal pulsegenerator (IPG), capable of burst mode, was implanted (EON®, ANSMedical, Plano, Tex., USA). The IPG was programmed with similarsettings, using a custom made programmer. The EON® was programmed withspike ramping (increasing amplitude of successive spikes within theburst) (FIG. 2 ). The ramp was added to the stimulation design to copynaturally occurring burst firing as closely as possible.

Results

None of the patients developed paresthesia during burst SCS treatment.All patients experienced reduced pain with burst SCS treatment. In somecases, pain suppression itself was not significantly better with burststimulation than with tonic stimulation, but the absence of paresthesiawas felt as a bonus to the patient. In one patient, however, paintreatment with tonic stimulation for two years prior to this study wasineffective in treating back pain, whereas treatment with burststimulation resulted in complete pain suppression. Another patientexperienced paresthesia along with pain in the absence of anystimulation, and experienced a complete suppression of both pain andparesthesia with burst SCS treatment. Furthermore, the data showed thatburst stimulation treats mechanical back pain, which is often acomponent or complication of failed back surgery, and nociceptive painbetter than tonic stimulation.

B. Example 2 Introduction

Spinal cord stimulation is commonly used for neuropathic painmodulation. The major side effect is the onset of paresthesias. Theapplicant describes a new stimulation design which suppresses the painwithout creating paresthesias.

Methods

Similarly, as described in Example 1, patients were implanted withdorsal column electrodes. 9 patients with neuropathic pain wereimplanted with paddle electrodes (Lamitrode 44, ANS Medical, Plano,Tex., USA) via a laminectomy: 3 on the cervical dorsal column at thelevel of C2 for cervicobrachialgia and 6 on the thoracic level at thelevel of T11 for lumboischialgia respectively. During the period ofexternal stimulation the patients received the classical tonicstimulation (40 or 50 Hz) and the burst stimulation (40 Hz burst with 5spikes at 500 Hz/burst).

Results

Pain scores were measured using a visual analogue scale (VAS) and aMcGill Shortform during pre-operative, tonic and burst stimulation.Paresthesias were scored as present or not present. Burst stimulationwas significantly better for pain suppression, both on VAS as shown inFIG. 3A (Z=2.37 p=0.018) as well as on the McGill Short form as shown inFIG. 3B (Z=1.96, p=0.050). Paresthesias were present in all 9 patientsduring tonic stimulation, during burst stimulation they were absent in67% or 6 of the 9 patients. Thus, the applicant presents a new way ofspinal cord stimulation using bursts in stead of tonic stimuli whichsuppresses neuropathic pain and does not create paresthesias.

III. Detailed Discussion of the Procedure

The following section more generally describes FIG. 4 or an example of aprocedure for pain treatment using burst SCS that optimizes thefollowing four parameters; location for electrode placement, a setand/or range of stimulation protocols that can most completely eliminatepain and paresthesia, a set and/or range of stimulation protocols thatrequires the lowest voltage, and a protocol that maintains treatmentefficacy over long periods of time. This treatment regimen as describedherein is designed to treat a patient's pain without paresthesia.

Implantation of Simulation Lead with Stimulation Electrodes (800)

One or more stimulation leads 14 are implanted such that one or morestimulation electrodes 18 of each stimulation lead 14 are positioned incommunication with the spinal cord (for the purposes described hereinand as those skilled in the art will recognize, when an embeddedstimulation system, such as the Bion®, is used, it is positioned similarto positioning the lead 14). Sites of interest include neuronal tissueassociated with the spinal cord, for example, the spinal cord areacorresponding to cervical vertebral segments C1 to C8, thoracicvertebral segments T1 to T12, or lumbar vertebral segments L1 and L2.

Techniques for implanting stimulation leads such as stimulation lead 14are known to those skilled in the art. In certain embodiments, one ormore stimulation electrodes 18 are positioned adjacent or near or indirect contact with the neuronal tissue of the spinal cord. Stimulationelectrodes 18 are commonly positioned external to the dura layersurrounding the spinal cord. Stimulation on the surface of the cord isalso contemplated, for example, stimulation may be applied to the spinalcord tissue as well as to the nerve root entry zone. Stimulationelectrodes 18 may be positioned in various body tissues and in contactwith various tissue layers; for example, subdural, subarachnoid,epidural, and subcutaneous implantation is employed in some embodiments.The electrodes are carried by two primary vehicles: percutaneous leadsand a laminotomy lead.

Percutaneous leads commonly have two or more equally-spaced electrodeswhich are placed above the dura layer through the use of a Touhy-likeneedle. For insertion, the Touhy-like needle is passed through the skinbetween desired vertebrae to open above the dura layer. An example of aneight-electrode percutaneous lead is an OCTRODE® lead manufactured byAdvanced Neuromodulation Systems, Inc. A Bion® stimulation systemmanufactured by Advanced Bionics Corporation is also contemplated. Apercutaneous stimulation lead 14, such as example stimulation leads 14a-d, includes one or more circumferential electrodes 18 spaced apartfrom one another along the length of stimulating portion 20 ofstimulation lead 14. Circumferential electrodes 18 emit electricalstimulation energy generally radially (i.e., generally perpendicular tothe axis of stimulation lead 14) in all directions.

In contrast to the percutaneous leads, laminotomy leads have a paddleconfiguration and typically possess a plurality of electrodes (forexample, two, four, eight, or sixteen) arranged in one or more columns.A laminotomy, paddle, or surgical stimulation lead 14, such as examplestimulation leads 14 e-i, includes one or more directional stimulationelectrodes 18 spaced apart from one another along one surface ofstimulation lead 14. Directional stimulation electrodes 18 emitelectrical stimulation energy in a direction generally perpendicular tothe surface of stimulation lead 14 on which they are located. An exampleof a sixteen-electrode laminotomy lead is shown in FIG. 6H. Anotherexample of a laminotomy lead is an eight-electrode, two columnlaminotomy lead called the LAMITRODE® 44, which is manufactured byAdvanced Neuromodulation Systems, Inc. Implanted laminotomy leads arecommonly transversely centered over the physiological midline of apatient. In such position, multiple columns of electrodes are wellsuited to address both unilateral and bilateral pain, where electricalenergy may be administered using either column independently (on eitherside of the midline) or administered using both columns to create anelectric field which traverses the midline. A multi-column laminotomylead enables reliable positioning of a plurality of electrodes, and inparticular, a plurality of electrode columns that do not readily deviatefrom an initial implantation position.

Laminotomy leads require a surgical procedure for implantation. Thesurgical procedure, or partial laminectomy, requires the resection andremoval of certain vertebral tissue to allow both access to the dura andproper positioning of a laminotomy lead. The laminotomy lead offers amore stable platform, which is further capable of being sutured inplace, which tends to migrate less in the operating environment of thehuman body. Depending on the position of insertion, however, access tothe dura may only require a partial removal of the ligamentum flavum atthe insertion site. In some embodiments, two or more laminotomy leadsmay be positioned within the epidural space, and the leads may assumeany relative position to one another.

Although various types of stimulation leads 14 are shown as examples,the claimed material contemplates stimulation system 10 including anysuitable type of stimulation lead 14 in any suitable number. Inaddition, stimulation leads 14 may be used alone or in combination. Forexample, medial or unilateral stimulation of the predetermined site maybe accomplished using a single electrical stimulation lead 14 implantedin communication with the predetermined site, while bilateral electricalstimulation of the predetermined site may be accomplished using twostimulation leads 14 implanted in communication with the predeterminedsite on opposite sides of, for example, the spinal cord. Multi-siteimplantation of stimulation leads can be used.

Coupling of Stimulation Source to Stimulation Lead (802)

In general terms, stimulation system 10 includes an implantableelectrical stimulation source 12 and one or more implantable electricalstimulation leads 14 for applying electrical stimulation pulses to apredetermined site. In operation, both of these primary components areimplanted in a subject's body, as discussed below. In certainembodiments, stimulation source 12 is coupled directly to a connectingportion 16 of stimulation lead 14. In other embodiments, stimulationsource 12 is incorporated into the stimulation lead 14 and stimulationsource 12 instead is embedded within stimulation lead 14. For example,such a stimulation system 10 may be a Bion® stimulation systemmanufactured by Advanced Bionics Corporation. Whether stimulation source12 is coupled directly to or embedded within the stimulation lead 14,stimulation source 12 controls the stimulation pulses transmitted to oneor more stimulation electrodes 18 located on a stimulating portion 20 ofstimulation lead 14, positioned in communication with a predeterminedsite, according to suitable stimulation parameters (e.g., duration,amplitude or intensity, frequency, pulse width, etc.). The predeterminedsite is the spinal cord in this example and may be the dorsal column ofthe spinal cord in a preferred embodiment.

In one embodiment, as shown in FIG. 5A, stimulation source 12 includesan implantable pulse generator (IPG). In another embodiment, as shown inFIG. 5B, stimulation source 12 is capable of wireless communicationsand, preferably, is capable of being recharged using inductive couplingwith an external charging device. An example of such a stimulationsource is the Eon® System available from Advanced NeuromodulationSystems, Inc. In another embodiment, the IPG can be optimized for highfrequency operation as described in U.S. Published Application No.US20060259098, which is incorporated herein by reference. Afterimplantation, the stimulation source 12 receives wireless signals from awireless transmitter 22 located external to the person's body. Thewireless signals are represented in FIG. 5B by wireless link symbol 24.A doctor, the patient, or another user of stimulation source 12 may usea controller 26 located external to the person's body to provide controlsignals for operation of stimulation source 12. Controller 26 providesthe control signals to wireless transmitter 22, wireless transmitter 22transmits the control signals and power to the implanted pulse generator12, and pulse generator 12 uses the control signals to vary thestimulation parameters of stimulation pulses transmitted throughstimulation lead 14 to the predetermined spinal column site. Wirelesstransmitter 22 and controller 26 can be integrated within a singledevice and are commercially distributed with implantable pulse generatorproducts.

Activate Stimulation Source and Transmit Trial Stimulation Pulse (804)

Conventional neuromodulation devices can be modified to apply burststimulation to nerve tissue of a patient by modifying the softwareinstructions and/or stimulation parameters stored in the devices.Specifically, conventional neuromodulation devices typically include amicroprocessor and a pulse generation module. The pulse generationmodule generates the electrical pulses according to a defined pulsewidth and pulse amplitude and applies the electrical pulses to definedelectrodes. The microprocessor controls the operations of the pulsegeneration module according to software instructions stored in thedevice and accompanying stimulation parameters. An example of acommercially available neuromodulation device that can be modified orprogrammed to apply burst stimulation includes the EON®, manufactured byAdvanced Neuromodulation Systems, Inc.

These conventional neuromodulation devices can be adapted by programmingthe microprocessor to deliver a number of spikes (relatively short pulsewidth pulses) that are separated by an appropriate inter-spike interval.Thereafter, the programming of the microprocessor causes the pulsegeneration module to cease pulse generation operations for aninter-burst interval. The programming of the microprocessor also causesa repetition of the spike generation and cessation of operations for apredetermined number of times. After the predetermined numbers ofrepetitions have been completed, the microprocessor can cause burststimulation to cease for an amount of time and resume thereafter.

Also, in some embodiments, the microprocessor could be programmed tocause the pulse generation module to deliver a hyperpolarizing pulsebefore the first spike of each group of multiple spikes. Themicroprocessor can be programmed to allow the various characteristics ofthe burst stimulus to be set by a physician to allow the burst stimulusto be optimized to treat the patient's pain. For example, the spikeamplitude, the inter-spike interval, the inter-burst interval, thenumber of bursts to be repeated in succession, the amplitude of thevarious pulses, and other such characteristics could be controlled usingrespective parameters accessed by the microprocessor during burststimulus operations. These parameters could be set to desired values byan external programming device via wireless communication with theimplantable neuromodulation device.

In another embodiment, a neuromodulation device can be implemented toapply burst stimulation using a digital signal processor and one orseveral digital-to-analog converters. The burst stimulus waveform couldbe defined in memory and applied to the digital-to-analog converter(s)for application through electrodes of the medical lead. The digitalsignal processor could scale the various portions of the waveform inamplitude and within the time domain (e.g., for the various intervals)according to the various burst parameters. A doctor, the patient, oranother user of stimulation source 12 may directly or indirectly inputstimulation parameters to specify or modify the nature of thestimulation provided.

Examples of burst stimulation are found in U.S. Published ApplicationNo. US20060095088, and incorporated herein by reference in its entirety.The burst stimulation may generate bursts of a plurality of electricalpulses with an inter-burst frequency in the range of about 1 Hz to about100 Hz, more particular, in the range of about 1 Hz to about 50 Hz, andmore particularly, about 40 Hz. The inter-burst interval has a durationin the range of about 1 milliseconds to about 5 seconds, morepreferably, about 10 milliseconds to about 300 milliseconds. Theinter-burst interval need not be constant and can be varied in aprogrammable manner or varied pseudo-randomly by the pulse generator(e.g., random or irregular harmonics).

In one embodiment the initial stimulation protocol in step 804 will be anon-saturating stimulation protocol that only partially eliminates painsensation and/or paresthesia. For example, a non-saturating protocol maybe created by employing voltages or stimulation protocols known not tobe completely effective in eliminating pain and/or paresthesia. In someembodiments the initial stimulation protocol in step 804 may involvetonic mode or burst mode stimulations. Using such non-saturatingprotocols, a location of maximum efficacy may be ascertained, withregards to the location of stimulation lead 14 and/or the differentialactivation of various stimulation electrodes 18. In other embodiments, aburst stimulation protocol may be designed for the patient at step 804wherein a voltage is applied that only partially eliminates painsensation and/or paresthesia, and various burst mode stimulationparameters are tested in order to determine a protocol of maximumefficacy. Once an optimal location and protocol have been determined,the voltage may be adjusted to completely eliminate sensation of painand paresthesia. In other embodiments, subsequent to location selection,step 804 may include the application of a saturating stimulationprotocol that reduces pain and paresthesia as completely as possible.

Assessment of Pain (806)

Those skilled in the art recognize that there are many methods to assessand quantify the patient's experience of pain. One example of a methodfor pain measurement is the use of the Visual Analog Scale (VAS). In theVAS patients are asked to rank their pain by making a mark on a bar thatis labeled “no pain” on one end, and “pain as bad as possible” on theother end. Patients may mark the bar anywhere between the two oppositepoles of perceived pain sensation. This mark can then be given anyquantitative value such as fractional, decimal, or integer values by theclinician and used as a semi-quantitative pain measurement. Another painmeasurement scale is the McGill Pain Questionnaire (SF-MPQ) thatprovides the patient with descriptors and the patient to rates theseverity or intensity of the pain on a scale of 0=none, 1=mild,2=moderate, or 3 severe. Other various tests for pain severity can alsobe used in which patients may rank their pain on a scale between zeroand ten, by a scale of faces depicting various emotions from happy tovery sad and upset, and by answering a variety of questions describingthe pain. In preferred embodiments, the patient's pain is assessed priorto and during the trial implantation procedure, for example prior toprocess 800, and then again at process 806. In other embodiments,informal subjective questioning of the person, and/or formal subjectivetesting and analysis may be performed to determine whether the subject'spain has sufficiently improved throughout the intra-implantation trialstimulation.

In some embodiments, it is considered that several cycles ofintra-implantation trials may be required. A comparison of the patient'sperceived pain between multiple cycles of intra-implantation trialstimulation will be used to determine the optimal location andstimulation protocol. In further embodiments, steps 804 through 808represent a repetitive cycle that ends when an optimal location andprotocol have been selected. In some embodiments, once the stimulationlead 14 has been properly positioned such that subject's perception ofpain is improved or absent, intra-implantation stimulation may beconsidered complete. It is contemplated that stimulation parameters maybe modified to maximize the effectiveness of the therapy both prior toand subsequent to the end of the intra-implantation trial stimulations.

In addition to utilizing pain scores and grading and objective measuresincluding use of additional pain medications (e.g., reduction in theamount of medication consume or elimination of the consumption of painmedications), other methods to determine improvement of a patient's painmay comprise administering various standardized questionnaires or teststo determine the patient's neuropsychological state. It is well known bythose in the art that depression is the most common emotionaldisturbance in patients with chronic pain. Such neuropsychologicaltesting can include, but are not limited to (i.e., Minnesota MultiphasicPersonality Inventory, Beck Depression Inventory, Mini-Mental StatusExamination (MMSE), Hamilton Rating Scale for Depression, Wisconsin CardSorting Test (WCST), Tower of London, Stroop task, MADRAS, CGI, orN-BAC).

Adjustment of Stimulation Parameters and/or Lead Location (808)

If the subject's pain has not sufficiently improved at process 806, orif the reduction of pain and paresthesia is determined to be incompleteor inadequate during the intra-implantation trial stimulation procedure,stimulation lead 14 may be moved incrementally or even re-implanted, oneor more stimulation parameters may be adjusted, or both of thesemodifications may be made at process 808 and the trial stimulation andanalysis repeated until the pain has sufficiently improved withoutparesthesia. In other embodiments, adjustments may be made at process808 even when complete reduction of pain and paresthesia is noted. Forexample, further refinement of electrode location may be desired.

Implantation of Stimulation Source (810)

In some embodiments the intra-trial stimulation period is determined tobe complete during process 806. In other embodiments, theintra-implantation trial stimulation is not performed, and the methodproceeds from process 802 to 810. Once the location for the stimulationlead 14 has been determined, the stimulation lead may be properlyimplanted and secured and a stimulation source 12 may be surgicallyimplanted at process 810. Techniques for implanting stimulation sourcessuch as stimulation source 12 are known to those skilled in the art. Fornon-embedded systems, the implant site is typically a subcutaneouspocket formed to receive and house stimulation source 12. The implantsite is usually located some distance away from the insertion site, suchas in or near the lower back or buttocks.

Tunneling of Stimulation Lead to Stimulation Source (812)

Where stimulation lead 14 includes connecting portion 16, connectingportion 16 may be tunneled, at least in part, subcutaneously to theimplant site of stimulation source 12 at step 812. Some embodiments mayuse a non-implantable stimulation source.

Input of Parameters to Stimulation Source (814)

During process 814, a doctor, the patient, or another user ofstimulation source 12 may directly or indirectly input stimulationparameters for controlling the nature of the electrical stimulationprovided to the target spinal tissue area, if not already set during anyintra-implantation trial stimulation period. Where appropriate,post-implantation trial stimulation may be conducted to determine theefficacy of various types of burst stimulation. Examples of efficacymetrics may include the minimum required voltage for a given protocol toachieve maximum and/or complete reduction of pain and or paresthesia.Efficacy metrics may also include a measurement of the presence and/ordegree of habituation to a given protocol over one or more weeks ormonths, and any necessary modifications made accordingly. Suchassessments can be conducted by suitable computer programming, such asthat described in U.S. Pat. No. 5,938,690, which is incorporated byreference here in full. Utilizing such a program allows an optimalstimulation pattern to be obtained at minimal voltages. This ensures alonger battery life for the implanted systems. Furthermore, painassessment as described above may be preformed to determine theefficiency of the protocol and based upon the assessment the stimulationparameters may be optimized or modified to achieve more efficient paincontrol.

In certain embodiments, it may be desirable for the patient to controlthe therapy to optimize the operating parameters to achieve increased oroptimized pain management or treatment. For example, the patient canalter the pulse frequency, pulse amplitude and pulse width using a handheld radio frequency device that communicates with the IPG. Once theoperating parameters have been altered by the patient, the parameterscan be stored in a memory device to be retrieved by either the patientor the clinician. Yet further, particular parameter settings and changestherein may be correlated with particular times and days to form apatient therapy profile that can be stored in a memory device.

Although example steps are illustrated and described, the claimedmaterial contemplates two or more steps taking place substantiallysimultaneously or in a different order. In addition, the claimedmaterial contemplates using methods with additional steps, fewer steps,or different steps, so long as the steps remain appropriate forimplanting stimulation system 10 into a person for electricalstimulation of the a predetermined site, such as, for example the dorsalcolumn at the cervical area to treat pain without paresthesia. In someembodiments the level of the spinal cord in which the stimulation is tooccur consists of segments T8-T11. In other embodiments the level of thespinal cord in which the stimulation is to occur consists of segments C2or C3.

IV. Types of Pain to be Treated

Burst firing is a more effective treatment for many neurologicalconditions as shown in this application as well as U.S. PublishedApplication No. 20060095088. It is also known to one skilled in the artthat burst stimulation is a more powerful activator of inhibition thantonic stimulation (Kim and McCormick, 1998).

Mechanistically, it is known that nociceptive neurons in the dorsalcolumn fire in burst mode (Lopez-Garcia et al., 1994). Lamina I and IIreceive predominantly nociceptive input (Ruscheweyh and Sandkuhler,2002). Most burst firing is noted in lamina II (Ruscheweyh andSandkuhler, 2002). Projection neurons in lamina I that fire in burstmode (Ruscheweyh et al., 2004) receive afferent C-fibers. It is knownthat a good correlation exists between the reported pain sensation andthe activity evoked in the afferent C-fibers (Olausson, 1998). Thus, itis envisioned that the burst type therapeutic stimulation systemdescribed herein will more efficient and effective at treating paincompared to typical tonic type SCS protocols.

Pain of a moderate or high intensity is typically accompanied byanxiety. Thus, one of skill in the art is cognizant that pain may havedual properties, for example sensation and emotion. Chronic pain can beassociated with several factors that include, but are not limited tolassitude, sleep disturbance, decreased appetite, loss of taste forfood, weight loss, diminished libido, constipation, or depression. Thus,in certain embodiments, in connection with improvement the electricalstimulation may have a “brightening” effect on the person such that theperson looks better, feels better, moves better, thinks better, eatsbetter, sleeps better, and otherwise experiences an overall improvementin quality of life.

In some embodiments, therapeutic stimulation system may be used to treatacute pain. Acute pain is transient in nature and generally consideredby those skilled in the art to be an important adaptive feature ofanimal survival. It is usually associated with an immediate injuriousprocess such as soft tissue damage, infection, or inflammation andserves the purpose of notifying the animal of the injurious condition,thus allowing for treatment or preventing further injury. In most casesof acute pain, adequate treatment may be obtained through theadministration of analgesic drugs. In some circumstances however,treatment of acute pain by drug delivery is either sub-optimal due topotential side-effects, or not possible. Examples include patients withhistories of drug abuse, contraindications with other necessary drugs,allergies or liver problems, and women in childbirth.

A common method for pain treatment during childbirth is the use ofepidural administration of drugs via injection or catheterization. Theadministration of anaesthetic or analgesic drugs via epidural has manydrawbacks. In addition to all of the potential negative side effects thedrug may have on the mother, there are potential complications for thechilbirth and early childhood development as well. For example the useof epidurals has been negatively correlated with vaginal birth outcomesin humans (Roberts et al., 2000). It has also been found that use ofepidurals is positively correlated with an early abandonment ofbreastfeeding in human infants (Torvaldsen et al., 2006). Additionallymany women find the analgesic effects of epidurals insufficient to treattheir pain both during and after childbirth. Because of the nonspecificeffects of the drugs commonly used, high dosages will cause non-specificnumbness and muscular weakness, which can interfere with the normalbirthing process. Burst SCS during childbirth may prove effective inalleviating pain completely without causing side effects such asmuscular weakness in the mother, and without adversely affecting thechild during or after childbirth.

In some embodiments, the therapeutic stimulation system may be used totreat chronic pain. As many as one in five people in the world currentlysuffer from chronic pain. Some forms of chronic pain are obviouslyassociated with a chronic injury condition that may or may not betreatable. Other forms of chronic pain such as neuropathic and phantompain may not be obviously associated with a continuing tissue injury andare discussed in greater detail below. All of the different forms ofchronic pain are similar in that they at least involve activation ofnociceptive fibers in the peripheral nervous system and subsequently,nociceptive central fibers in the dorsal spinal cord. All forms ofchronic pain are also similar in that they provide little value to theperson experiencing them, and may substantially reduce that person'squality of life.

It is known to one skilled in the art that administration of analgesicdrugs in the treatment of chronic pain is almost always non-optimal.There are several reasons for this. First of all, most drugs used in thetreatment of pain become less effective in treating pain over longperiods of time such as in chronic pain conditions. Secondly, many drugsthat treat pain are addictive to the patient, and may result insubstance abuse and or withdrawal symptoms by the patient subsequent totreatment. Thirdly, many drugs used to treat pain produce unwanted sideeffects that are increased during long term use. Such side effects caninclude toxic effects on the patient's body such as the nervous systemitself and other internal organs such as the heart, liver, and kidneys.Overdoses of many analgesic drugs can be fatal.

In some embodiments, the therapeutic stimulation system may be used totreat neuropathic pain. Neuropathic pain is pain that results fromdamage to the nervous system itself. It may exist independently of anyother form of tissue injury outside of the nervous system. It can becaused by myriad factors such as disease (HIV, Herpes, Diabetes, Cancer,autoimmune disorders), acute trauma (surgery, injury, electric shock),or chronic trauma (repetitive motion disorders, chemical toxicity suchas alcohol, chemotherapy, or heavy metals). Neuropathies can originateanywhere in the central or peripheral nervous system, but only in somecases does this produce neuropathic pain. One notable feature ofneuropathic pain is that it often involves a combined pain sensation.The sensation is often described as burning, shocking, or tingling pain.It is theorized that these unique pain sensations are due to thecombined activation of both nociceptive and non-nociceptive sensorypathways from the same region of the body. According to the previouslydescribed tenets of Gate Control Theory, nociceptive and non-nociceptivefibers from a given dermatome normally mutually inhibit one another uponactivation and therefore the two subsequent sensations should rarely ifever co-exist temporally in the brain. Thus, neuropathies often producedisturbing and confusing pain sensations that are quite unlike othercommon forms of pain.

In some embodiments, the therapeutic stimulation system may be used totreat phantom pain. Phantom pain is a condition whereby the patientsenses pain in a part of the body that is either no longer physicallypresent due to amputation, or is known to be completely insensate due tototal peripheral nerve destruction. When severe damage occurs inperipheral tissue such that nociceptive nerve endings are destroyed, butthe nociceptive neuron itself is not severed from the spinal cord,phantom pain may develop. In phantom pain, the tonic firing rate of thenociceptive sensory neurons increases (Yamashiro et al., 2003), as doesthe amount of burst firing in the deafferented receptive fields (Rinaldiet al., 1991; Jeanmonod et al., 1996; Radhakrishnan et al., 1999) in thesomatosensory thalamic nuclei (Rinaldi et al., 1991; Lenz et al., 1998),as well as activity in the in the intralaminar nuclei (Weigel and Krauss2004). Synchrony in firing is also increased. This is similar to what isseen in animal neuropathic pain models (Lombard and Besson 1989;Nakamura and Atsuta 2004) (Yamashiro et al., 1991). These resultssuggest that in phantom pain, decreased spike frequency adaptation andincreased excitability develops after injury to sensory neurons. Throughdecreased Ca²⁺ influx, the cell becomes less stable and more likely toinitiate or transmit bursts of action potentials (McCallum et al.,2003).

In some embodiments, the therapeutic stimulation system may be used totreat hyperalgesia and or allodynia. Hyperalgesia is an increasedsensitivity to nociceptive or painful stimuli that occurs subsequent totissue injury or nociceptive pathway activation. Allodynia is verysimilar to hyperalgesia and describes a condition whereby normallynon-noxious stimuli are perceived as painful. Both hyperalgesia andallodynia can be divided into primary and secondary categories orconditions.

Primary hyperalgesia and allodynia is an increase in sensitivity topainful and previously non-painful stimuli in a region of the body thathas undergone tissue injury. Primary hyperalgesia is due in part tochanges in the spinal cord that are mediated by the input from primaryafferent C-fiber nociceptors (Ikeda et al., 2006). Signals from higherbrain regions are also sent to the spinal cord that can decrease primaryhyperalgesia (Vanegas, 2004). As such primary hyperalgesia may betreatable by burst SCS.

Secondary hyperalgesia is an increase in pain sensitivity globally andrequires descending input into the periphery from various painprocessing centers in the brain. Pain processing centers in the brainnormally require an initial nociceptive stimulus from the periphery inorder to induce hyperalgesia. Moreover, all secondary hyperalgesiasignals must pass back through the spine to sensitize the peripheralnociceptors and thus induce the hyperalgesia. Therefore, any therapythat blocks the nociceptive signal at the level of the spinal cord maybe either block secondary hyperalgesia in the first place in acute paintreatments, or terminate hyperalgesia upon continuous treatment ofchronic pain. Since burst stimulation is a more powerful activator ofinhibition than tonic stimulation, it may suppress this burst firingnociceptive pathway, whereas tonic stimulation may not.

REFERENCES

All patents and publications mentioned in the specification areindicative of the levels of those skilled in the art to which theclaimed material pertains. All patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference.

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Although the claimed material and its advantages have been described indetail, it should be understood that various changes, substitutions andalterations can be made herein without departing from the claimedmaterial as defined by the appended claims. Moreover, the scope of thepresent application is not intended to be limited to the particularembodiments of the process, machine, manufacture, composition of matter,means, methods and steps described in the specification. As one willreadily appreciate from the disclosure, processes, machines,manufacture, compositions of matter, means, methods, or steps, presentlyexisting or later to be developed that perform substantially the samefunction or achieve substantially the same result as the correspondingembodiments described herein may be utilized. Accordingly, the appendedclaims are intended to include within their scope such processes,machines, manufacture, compositions of matter, means, methods, or steps.

What is claimed is:
 1. A method of treating pain without paresthesiacomprising the steps of: implanting at least an electrical lead within apatient such that at least one electrode of the electrical lead isdisposed within an epidural space of a vertebral segment, wherein thevertebral segment corresponds to a thoracic vertebral segment or alumbar vertebral segment; selecting one or more operating parameters foran electrical spinal cord stimulation system that define burststimulation that is effective for treating pain of the patient, wherein,when generated by the electrical spinal cord stimulation system, theburst stimulation comprises a plurality of electrical pulses thatexhibit a pulse rate between 500 Hz and 10,000 Hz; programming theelectrical spinal cord stimulation system to generate the plurality ofelectrical pulses according to the one or more operating parameters; andactivating the electrical spinal cord stimulation system to deliver theplurality of electrical pulses to the at least one electrode disposedwithin the epidural space of the vertebral segment in accordance withthe one or more operating parameters to stimulate nerve tissue of thepatient to treat the patient's pain without paresthesia, wherein thenerve tissue comprises dorsal fibers of the spinal cord associated withthe thoracic vertebral segment or the lumbar vertebral segment.
 2. Themethod of claim 1, wherein the plurality of electrical pulses include aseries of electrical pulses with increasing amplitude.
 3. The method ofclaim 1, wherein the burst stimulation includes multiple bursts ofelectrical pulses with an inter-burst frequency in a range of about 1 Hzto about 100 Hz.
 4. The method of claim 3, wherein the inter-burstfrequency range is about 40 Hz to about 50 H.
 5. The method of claim 1,wherein the burst stimulation is preceded by a pre-conditioningelectrical pulse.
 6. The method of claim 5, wherein the pre-conditioningelectrical pulse is a hyper-polarizing pulse.
 7. The method of claim 1,wherein the plurality of electrical pulses of the burst stimulationcomprises a group of at least two electrical pulses separated by a timeinterval of between about 0.1 and about 10 milliseconds.
 8. The methodof claim 7, wherein the burst stimulation further comprises two or moresuch groups.
 9. The method of claim 7 or 8, wherein a pulse frequency ofthe at least two electrical pulses within at least one groupconsecutively increases.
 10. The method of claim 8, wherein the timebetween two successive groups is between 1 millisecond and 5 seconds.11. The method of claim 8, wherein the time between two successivegroups is between about 10 milliseconds to about 300 milliseconds. 12.The method of claim 8, an amplitude of successive electrical pulsesincreases within a group.
 13. The method of claim 1, wherein theplurality of electrical pulses include a plurality of electrical pulseswith increasing amplitude.
 14. The method of claim 1, wherein theplurality of electrical pulses exhibit a fixed inter-pulse interval. 15.The method of claim 1, wherein the plurality of electrical pulsesexhibit variations in inter-pulse intervals.
 16. The method of claim 1,wherein the plurality of electrical pulses exhibit pseudo-randomvariations in inter-pulse intervals.